A randomized, controlled trial of interventions to improve adherence to isoniazid therapy to prevent tuberculosis in injection drug users.

PURPOSE: To determine the effect of several interventions on adherence to tuberculosis preventive therapy. METHODS: We conducted a randomized trial with a factorial design comparing strategies for improving adherence to isoniazid preventive therapy in 300 injection drug users with reactive tuberculin tests and no evidence of active tuberculosis. Patients were assigned to receive directly observed isoniazid preventive therapy twice weekly (Supervised group, n = 99), daily self-administered isoniazid with peer counseling and education (Peer group, n = 101), or routine care (Routine group, n = 100). Patients within each arm were also randomly assigned to receive an immediate or deferred monthly $10 stipend for maintaining adherence. The endpoints of the trial were completing 6 months of treatment, pill-taking as measured by self-report or observation, isoniazid metabolites present in urine, and bottle opening as determined by electronic monitors in a subset of patients. RESULTS: Completion of therapy was 80% for patients in the Supervised group, 78% in the Peer group, and 79% in the Routine group (P = 0.70). Completion was 83% (125 of 150) among patients receiving immediate incentives versus 75% (112 of 150) among patients with deferred incentives (P = 0.09). The proportion of patients who were observed or reported taking at least 80% of their doses was 82% for the Supervised arm of the study, compared with 71% for the Peer arm and 90% for the Routine arm. The proportion of patients who took 100% of doses was 77% for the Supervised arm (by observation), 6% for the Peer arm (by report), and 10% for the Routine arm (by report; P <0.001). Direct observation showed the median proportion of doses taken by the Supervised group was 100%, while electronic monitoring in a subset of patients showed the Peer group (n = 27) took 57% of prescribed doses and the Routine group (n = 32) took 49% (P <0.001). Patients in the Routine arm overreported adherence by twofold when data from electronic monitoring were used as a gold standard. There were no significant differences in electronically monitored adherence by type of incentive. CONCLUSION: Adherence to isoniazid preventive therapy by injection drug users is best with supervised care. Peer counseling improves adherence over routine care, as measured by electronic monitoring of pill caps, and patients receiving peer counseling more accurately reported their adherence. More widespread use of supervised care could contribute to reductions in tuberculosis rates among drug users and possibly other high-risk groups.

Serotonin syndrome caused by overdose with paroxetine and moclobemide.

Well known clinical syndromes can be produced by overdose with more commonly ingested substances such as opiates or tricyclic antidepressants. A case of a much more unusual syndrome presenting to the accident and emergency department resulting from overdose with a combination of tablets is reported. The clinical presentation of serotonin syndrome and its management are described. This resulted from acute ingestion of paroxetine, a selective serotonin reuptake inhibitor, and moclobemide, a monoamine oxidase inhibitor.

Simultaneous differentiation and quantitation of erythroblasts and white blood cells on a high throughput clinical haematology analyser.

After the neonatal period, the presence of nucleated red blood cells (NRBC) in peripheral blood is indicative of pathology. Despite the clinical utility of such measurements, automated NRBC counting has hitherto not been available on routine automated blood cell counting analysers. To address this, an automated method for the analysis of NRBC was developed and incorporated into the Abbott Cell Dyn 4000 (CD4000) haematology analyser. The system white blood cell (WBC) reagent was specifically formulated to preserve concomitantly white blood cell (WBC) morphology, rapidly lyse red blood cell and NRBC membranes, and subsequently stain NRBC nuclei with a nucleotide specific fluorochrome dye (Kim et al. 1996a). The fluorochrome itself does not permeabilize the membrane of intact viable white blood cells. The sample is processed by flow cytometry and the signals generated from an argon-ion laser light source are analysed. Axial light loss (AxLL), intermediate angle light scatter (IAS) and red fluorescence (FL3) are used to discriminate between particles of various types. By using these discriminators in a three-dimensional approach, NRBC from a discrete cluster which can easily be separated from leucocytes and enumerated as a distinct cell population during the optical WBC differential analysis. Consequently, accurate absolute WBC counts and differentials can be obtained even in the presence of NRBC. Background 'noise' (both fluorescent and non-fluorescent) from platelets. Howell-Jolly bodies, basophilic stippling, RNA from lysed reticulocytes, and DNA from leucocyte and megakaryocytic fragments are essentially eliminated (Kim et al. 1996b). While the membranes of intact and viable leucocytes remain impermeable to the passage of the fluorochrome stain, leucocytes with damaged membranes are permeable to the dye and generate FL3+ signals. Such cells, which are commonly seen as a consequence of sample ageing as well as in some distinctive pathologies, are identified by the algorithm (using their AxLL signal size) and are labelled as non-viable. Moreover, because non-viable leucocytes are retained in the WBC count and differential analyses, the CD4000 is further able to provide both numerical and graphical data regarding the relative frequency of viable and non-viable components. This additional information can serve as valuable 'decision-drivers' in the laboratory data review process.

Unusual acute and chronic complications of malaria.

32 cases (21 acute severe malaria and 11 chronic malaria syndrome), who developed unusual complications and/or manifestations are reported. The acute manifestations were unexplained tachypnoea 4, pulmonary oedema 5 and shock due to multiple organ dysfunction syndrome 3, melena 2 and E coli septicaemia in one. The other features were concomitant salmonellosis 2, meningitis 1, renal failure 3, hepatorenal syndrome 2, hepatitis like illness 7, neck stiffness with normal CSF 3, urticaria and subconiunctival haemorrhage 2 each, apyrexial spell with anaemia 4, thromocytopenia 3, and hypoglycaemia 3 (two pretreatment and one while on quinine in 5% glucose drip). The chronic syndrome noted were hyperreactive malaria syndrome (Tropical splenomegaly) 3, repeated haemolysis 2, chronic simple malaria with positive parasitaemia and normal Igm levels 4, and cerebellar ataxia with tremors 3. Bone marrow in these cases was hypercullular with increase plasma cells. Liver biopsy revealed lymphocytic infiltration. There was no case with permanent neurogical deficit. All patients with pulmonary oedema and multiple organ dysfunction died but chronic syndrome patients recovered fully. Early recoginition of atypical manifestation and prompt treatment will decrease the mortality and morbidity due to malaria.

Formulation of the reference Indian adult: anatomic and physiologic data.

Data on heights and weights of Indian males and females of various ages are presented. The weights of specific organs obtained from post-mortem records of accident cases of Indian adults and children are also presented to provide some inputs towards formulation of an Indian Reference Man for radiation protection purposes. An intercomparison of the present data with the data available from other sources including those for ICRP Reference Man, Woman, and Child has been made. The daily intakes of air, water, and dietary constituents of an average Indian adult are also given.